来曲唑对子宫肌瘤细胞增殖凋亡及cAMP-PKA信号通路的影响

Effects of Letrozole on Proliferation and Apoptosis of Uterine Fibroids and cAMP-PKA Signaling Pathway

目的探讨来曲唑对子宫肌瘤细胞增殖凋亡及cAMP-PKA信号通路的影响。方法分离子宫肌瘤细胞,来曲唑(10-7、10-6、10-5 mol·L-1)处理48 h。采用CCK-8法检测细胞增殖能力;流式细胞技术检测细胞凋亡;RT-PCR法检测Bcl-2、caspase-3 mRNA表达;WB检测MMP-2、TIMP-2、cAMP、PKA蛋白表达量。结果来曲唑以浓度依赖的方式明显下调细胞增殖,明显增加细胞凋亡(P<0.05);来曲唑以浓度依赖的方式明显下调子宫肌瘤细胞bcl-2、MMP-2、cAMP、PKA表达,上调子宫肌瘤细胞caspase-3、TIMP-2表达(P<0.05)。结论来曲唑可促进细胞凋亡、抑制细胞增殖,影响cAMP-PKA信号通路,且呈现浓度依赖性。

Objective To investigate the effects of letrozole on the proliferation and apoptosis of uterine fibroid cells and cAMP-PKA signaling pathway.Methods Uterine fibroid cells were isolated and treated with letrozole(10-7,10-6,10-5 mol·L-1)for 48h.CCK-8 method was used to detect cell proliferation ability.flow cytometry was used to detect apoptosis.RT-PCR method was used to detect Bcl-2 and caspase-3 mRNA expression.WB was used to detect MMP-2,TIMP-2,cAMP and PKA protein expression.Results Letrozole significantly reduced cell proliferation and significantly increased apoptosis in a concentration-dependent manner(P<0.05).Letrozole significantly reduced the expression of bcl-2,MMP-2,cAMP,PKA in uterine fibroid cells and up-regulated the expression of caspase-3 and TIMP-2 in uterine fibroid cells in a concentration-dependent manner(P<0.05).Conclusion Letrozole can promote apoptosis,inhibit cell proliferation,affect the cAMP-PKA signaling pathway,and appears concentration-dependent.